Issues concerning methodology on statistical evaluation of bridging evidence for registration of pharmaceutical products in the new region are addressed. These issues include design, inclusion and exclusion criteria, selection of treatment groups, choice of endpoints, study duration, consideration of type I and type II error for evaluation of bridging evidence, determination of sample size and statistical methods for analysis of bridging data. Statistical interpretation of extrapolation of bridging evidence from the original region to the new region in terms of similarity is given. For bridging evidence in the Clinical Data Package, the randomized parallel dose-response designs stratified to the ethnic factors and region will generate internally valid data for evaluating similarity on dose response, efficacy and safety concurrently between the regions for assessment of the ability of extrapolation to the new region. Statistical estimation and hypotheses for evaluation of bridging evidence will be given. It is recommended that the confidence interval approach be used for assessment similarity between the foreign and new regions.

Other issues such as endpoints, trial duration, and sample size determination will be also discussed. In general, the required sample size for evaluation of similarity between the regions is larger than that needed for evaluation of treatment effects only. For the bridging studies performed in the new region, although the hypotheses for assessment of bridging evidence remain the same, the data of the foreign and new regions are not generated concurrently. A model-based Bayesian approach for incorporating the foreign bridging information into the data generated by the local bridging study is suggested.

One can utilize either the posterior probability of similarity between the foreign and new regions or the highest posterior density interval for evaluating the strength of bridging evidence. Issues on study design, endpoints, and trial duration for the local bridging study will be also addressed. In general, the required sample size for the bridging trials in the new region is inversely proportional to the strength of the evidence from the data generated in the original region.

Key words: Extrapolation, Similarity, Design, Bayesian Approach

The views expressed in this presentation are professional opinions of the presenter and may not necessarily represent the position of the National Health Research Institutes, Taiwan.